title: PP2A inhibitors induce apoptosis in pancreatic cancer cell line PANC-1 through persistent phosphorylation of IKKα and sustained activation of the NF-κB pathway.
abstract: Serine/threonine protein phosphatase 2A (PP2A), is thought to be a cancer suppresser, as inhibition of PP2A can induce phosphorylation and activation of substrate kinases, most of which can accelerate growth. Interestingly, cantharidin potently inhibits PP2A but efficiently represses various cancer cells. In the present study, we found that PP2A inhibitors, cantharidin or Okadaic acid, inhibited cell viability and triggered apoptosis in PANC-1 pancreatic cancer cell line dependent on PP2A/IKKα/IκBα/p65 NF-κB pathway. The activation of NF-κB pathway up-regulated downstream pro-apoptotic genes, TNF-α, TRAILR1 and TRAILR2, and triggered apoptosis through the extrinsic pathway, indicating that PP2A is a potential target for pancreatic cancer treatment.
authors.affiliation: Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Zheng
authors.initials: Z
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Zong
authors.forename: Feiran
authors.initials: F
authors.lastname: Gong
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jinghuan
authors.initials: J
authors.lastname: Lv
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Xie
authors.forename: Yujie
authors.initials: Y
authors.lastname: Sun
authors.forename: Yi
authors.initials: Y
authors.lastname: Miao
authors.forename: Min
authors.initials: M
authors.lastname: Tao
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.forename: Zekuan
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002193:Cantharidin / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D051550:I-kappa B Kinase / Q000187:drug effects / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D019319:Okadaic Acid / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D019319:Okadaic Acid; C496559:CHUK protein, human; D051550:I-kappa B Kinase; D054648:Protein Phosphatase 2; D002193:Cantharidin